Guide to Fentanyl: Addiction Signs, Symptoms, and Withdrawal

In 2016, fentanyl gained the infamous title of America’s deadliest drug with 18,355 attributed deaths in the U.S. that year compared to 15,961 deaths attributed to heroin.1 The number of opioid-related deaths involving fentanyl has increased dramatically in recent years, from 14.3% in 2010 to 59.8% in 2017.2

Fentanyl is a powerful synthetic opioid analgesic that has a very rapid onset and a short duration of effect. The primary use of fentanyl is for pain relief, but it is also used, off-label, as a procedural anesthetic.Fentanyl is more potent than many other major opioids used for pain control such as morphine, for which it is 50 to 100 times more potent.2,3

The DEA lists fentanyl as a Schedule II controlled substance, indicating it has a high potential for abuse and addiction. Pharmaceutical fentanyl is intended for hospital or other prescription use, however some of this otherwise licit supply may be diverted for nonmedical misuse.Pharmaceutical fentanyl may be administered via several different routes (e.g., oral, transdermal, injection) and is available under several different brand names, including Abstral, Actiq, Duragesic, Sublimaze, and Fentora.2,3,4,5

Development and Routes of Administration

Fentanyl was first synthesized in the 1960s and eventually introduced in a patch form, in lollipops, in lozenge forms, and more recently in a spray form, along with the more standard forms of administration, such as injections and pills.2,4,5

When used as intended, transdermal fentanyl patches are applied to the skin to provide potent and consistent relief of pain for as long as 72 hours.Lozenges dissolve in the mouth and are used in the treatment of breakthrough pain for patients that are already taking other opiates for severe pain, whereas the injected solution form can be used for pain relief and sedation before and during surgery.

How Fentanyl Affects the Mind and Body

Fentanyl is a synthetic opioid agonist. By binding to and activating certain types of opioid receptors in the body, fentanyl is able to modify the perception of pain signaling.

The activation of these receptors is also associated with increased dopamine activity in our brain reward centers, which is thought to underlie the reinforcement or rewarding feeling linked with opioid drug use. This increase in dopamine activity in these areas may be accompanied by a state of euphoria and relaxation. The association of these pleasurable feelings increases the incentive to repeat the action linked to the feeling in order to achieve this sensation.1,2

While it is an important, effective painkiller in several clinical scenarios, fentanyl—with its capacity to potently elicit the euphoric feelings associated with many other members of the opioid class of drugs—has decidedly pronounced abuse potential.2,3

Fentanyl Abuse

Illicitly manufactured fentanyl may be used via the same routes as heroin and, in fact, may be present as an adulterant in what is being distributed as heroin. The drug is often sold in a powder form and either injected into a vein, snorted, or smoked (but may also be dropped on blotter paper, administered via an eyedropper, or pressed into pills). Fentanyl is far more potent than heroin and results in many cases of overdose.2-4

Pharmaceutical fentanyl—such as transdermal fentanyl patches and troche/lozenge/lollipops—may also be diverted for illicit or nonmedical use. Users may attempt to extract the drug out of the patch and either inject or orally consume it, whereas lozenge and lollipop forms may be crushed or chewed to bypass the intended extended-release mechanisms prior to being consumed.2-4

People who abuse the drug by taking it without supervision are putting themselves at great risk. Due to the potency of fentanyl, the difference between the dose that is used for therapeutic reasons and a potentially fatal overdose is actually very small.2,6 Moreover, fentanyl users very quickly experience tolerance to even high doses, so doses that might produce a satisfactory high one week may not result in the same experience even just a few days later.  This situation is further complicated by individuals who mix fentanyl with heroin, alcohol, or central nervous system depressants, as overdose risks become compounded.

Potential Adverse Effects of Fentanyl

There are a number of potential side effects associated with fentanyl use. Commonly reported side effects include:1-5

  • Dizziness.
  • Fainting spells.
  • Changes in pupil size.
  • Vision changes.
  • Over-sedation.
  • Confusion.
  • Mood changes (e.g., anxiety, depression).
  • Unusual tiredness or weakness.
  • Ringing or pounding in the ears.
  • Chest tightness.
  • Slowed breathing.
  • Pale skin or changes in pallor.
  • Uncontrollable shaking of a part of the body.
  • Back pain.
  • Pain or cramps in other areas of the body.
  • Mouth sores or pain/irritation (with oral transmucosal use).
  • Nausea or vomiting.
  • Constipation.
  • Urinary changes.
  • Swelling of the ankles, feet, or hands.
  • Loss of appetite.
  • Weight loss.

More severe developments may include:1-5

  • Severe incoordination (ataxia).
  • Clumsiness or unsteadiness.
  • Problems walking.
  • Chronic, severe constipation.
  • Muscle twitching or jerking.
  • Irregular heartbeat.
  • Respiratory depression / labored breathing.
  • Seeing, hearing, or feeling things that are not there.
  • Decreased awareness or responsiveness.
  • Loss of consciousness.
  • Seizures.

Signs of a fentanyl overdose may include:1-5, 7

  • Confusion.
  • Severe respiratory depression.
  • Respiratory arrest.
  • Pinpoint pupils (or dilated pupils secondary to respiratory depression-related hypoxia).
  • Slowed heartbeat.
  • Low blood pressure.
  • Cold and clammy skin.
  • Stupor.
  • Skeletal muscle flaccidity.
  • Severe drowsiness or inability to be awakened.
  • Seizures.
  • Coma.

How Does Fentanyl Addiction Begin?

Because fentanyl is a pure opioid agonist, it is not unusual for anyone who uses the drug for any significant period of time for any reason to develop at least some magnitude of physical dependence to the drug.Though having a physical dependence to fentanyl is not necessarily the same thing as being addicted to it, physical dependence (and avoidance of the accompanying acute opioid withdrawal syndrome) may be a factor in the development of compulsive misuse of the drug and eventually addiction.

A risk of abuse and addiction may always be present with potent, full opioid agonists. A person may begin using fentanyl for medical purposes, but later increase use of the substance as tolerance develops. As the person begins using the substance outside of the prescription parameters, dependence grows. Coupled with accelerating use and growing physical dependence are the phenomena of withdrawal and withdrawal avoidance; it often doesn’t take long before the person is struggling with full-blown addiction.

Signs of Fentanyl Addiction

Aside from tolerance and withdrawal, there are different signs and symptoms that could point to a burgeoning fentanyl addiction. In addition to the aforementioned dual phenomenon of tolerance and withdrawal, the following items exemplify some of the criteria used to make a formal diagnosis of an opioid use disorder:

  • Spending a great deal of time trying to get, using, or recovering from using the drug
  • Desiring to decrease use but being unsuccessful at doing so
  • Taking fentanyl in larger amounts or over a longer time period of time than intended
  • Strong cravings or urges for continued fentanyl use
  • Use of fentanyl leads to the inability to fulfill major life obligations
  • Use of the drug in dangerous situations
  • Continuing to use in spite of negative repercussions socially, academically, or at work
  • Giving up activities that were once important
  • Continuing to use the drug, resulting in worsening physical or mental health

Beyond the diagnostic criteria, other signs or changes in behavior that may suggest the development of an addiction include:

  • Seeing different doctors to get different prescriptions for the medication.
  • Forging prescriptions.
  • Financial problems; stealing or borrowing money to pay for fentanyl.
  • A breakdown of interpersonal relationships as a result of fentanyl use.

Medical Detox

Many seeking to end their compulsive fentanyl or other opioid use do so under the supervision of a physician in a professional medical detox program.

During withdrawal management, people are often first stabilized with replacement opioid agonist therapy, in the form of buprenorphine or methadone. In some cases a tapering schedule of the replacement medication is initiated to slowly ease individuals off the drug over a scheduled period of time; others may be maintained on a replacement medication in the longer term.

The timeline for fentanyl withdrawal may vary greatly based on individual circumstances, such as the length of use, the average dose used, the degree of physiological dependence, the presence of any co-occurring mental health issues, and other physical and mental factors.2,6

Treatment beyond Just Medical Detox

While necessary and the first step in opiate addiction treatment, medical detox does not constitute treatment on its own. In order to achieve recovery, people struggling with fentanyl addiction must address the underlying issues that led to their abuse of the drug in the first place. Without comprehensive therapeutic care, individuals may be more likely to relapse to opiate use after detox.

Treatment for opiate addiction takes many forms, such as cognitive behavioral therapy (CBT), motivational interviewing, contingency management, group counseling, medication-assisted therapy, as well as several complementary, alternative, and holistic approaches to augment the therapeutic plan. It’s imperative to choose a treatment program that caters care to each individual. Treatment should also be adjusted as needed throughout the recovery process.



  1. American Academy of Family Physicians (AAFP). (2019). New Report Details 2011-2016 Fentanyl Overdose Death Rates.
  2. National Institute on Drug Abuse (NIDA). (2019). Fentanyl.
  3. U.S. Department of Justice. DEA. (2017). Drugs of Abuse, A DEA Resource Guide.
  4. U.S. National Library of Medicine. (2018). Fentanyl.
  5. Stanley, T. (2014). The Fentanyl Story.The Journal of Pain, 15(12): 1215-126.
  6. Davis, Kathleen (2019). Everything You Need to Know About Fentanyl. Medical News Today.
  7. U.S. Food and Drug Association (FDA). (2019). Fentanyl Citrate: Prescribing Information.
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